Cascaded immunotherapy with implantable dual-drug depots sequentially releasing STING agonists and apoptosis inducers

Kai Li, Xuan Yu, Yanteng Xu (), Haixia Wang, Zheng Liu, Chong Wu, Xing Luo, Jiancheng Xu, Youqiang Fang, Enguo Ju, Shixian Lv, Hon Fai Chan, Yeh-Hsing Lao, Weiling He (), Yu Tao () and Mingqiang Li ()
Additional contact information
Kai Li: Sun Yat-sen University
Xuan Yu: Sun Yat-sen University
Yanteng Xu: Sun Yat-sen University
Haixia Wang: Sun Yat-sen University
Zheng Liu: Sun Yat-sen University
Chong Wu: Xiamen University
Xing Luo: Sun Yat-sen University
Jiancheng Xu: Sun Yat-sen University
Youqiang Fang: Sun Yat-sen University
Enguo Ju: Sun Yat-sen University
Shixian Lv: Peking University
Hon Fai Chan: The Chinese University of Hong Kong
Yeh-Hsing Lao: The State University of New York
Weiling He: Xiamen University
Yu Tao: Sun Yat-sen University
Mingqiang Li: Sun Yat-sen University

Nature Communications, 2025, vol. 16, issue 1, 1-26

Abstract: Abstract Non-nucleotide stimulators of interferon gene (STING) agonists hold promise as immunotherapeutic agents for postsurgical adjuvant treatment of tumors. However, their limited effect duration hampers therapeutic effectiveness, necessitating prolonged administration of multiple doses that heightens infection risk and impacts patient compliance. Here, we develop an implantable dual-drug depot in a sandwich-like configuration, with a non-nucleotide STING agonist (MSA-2) in the outer layers of 3D-printed scaffolds and an immunogenic apoptosis inducer (doxorubicin, DOX) in the inner layer of electrospun fibers. We discover that MSA-2 can elicit endoplasmic reticulum stress-mediated and general immunogenic apoptosis of cancer cells. The stimulations with tumor-associated antigens and damage-associated molecular patterns from cancer cells, along with proinflammatory factors secreted by matured dendritic cells and M1-polarized macrophages, can depolymerize intracellular microtubules guiding activated STING trafficking towards lysosomes for degradation. Collectively, the dual-drug depots can initiate a long-lasting cascaded immunotherapy and chemotherapy, suppressing postsurgical tumor recurrence and metastasis.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56407-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56407-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56407-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().